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Milam A Brantley, Karan Uppal, Chunyu Ma, Anita Agarwal, Margaret A Pericak-Vance, William K Scott, Jonathan L Haines, Dean Jones, Sabrina L Mitchell; Metabolomics reveals changes in fatty acid metabolism in age-related macular degeneration patients. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1187. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To identify metabolic pathways altered in patients with age-related macular degeneration (AMD) and determine pathways specifically affected in intermediate AMD (IAMD) and neovascular AMD (NVAMD).
We performed untargeted metabolomics using high-resolution LC-MS on plasma from 191 AMD patients (IAMD=91, NVAMD=100) and 195 controls. The mass spectrometer was set to capture mass to charge ratio from 85 to 1985 over 10 minutes. Metabolic features were extracted using apLCMS and xMSanalyzer. Partial least squares discriminant analysis (PLS-DA) was used to identify features that discriminate between groups in each comparison. Those features with a variable importance for projection (VIP) ≥ 2 were further assessed using linear models for microarray data (limma) to prioritize features for verification by tandem mass spectrometry. Additionally, pathway analysis was performed with Mummichog on those features identified by PLS-DA with VIP ≥ 1.5.
After data preprocessing and filtering, more than 6,300 features were available for downstream analyses in each of the three comparisons. When comparing AMD patients to controls, 351 discriminating features were identified. The carnitine shuttle (p<1.0 x 10-5) and prostaglandin formation from dihomo-gamma-linoleic acid (p=1.1 x 10-4) pathways were altered in AMD patients compared to controls. When comparing IAMD patients to controls, 284 discriminating features were identified. Seven pathways were altered in IAMD patients compared to controls. The two most significant were the carnitine shuttle (p=0.015) and saturated fatty acid beta-oxidation (p=0.026) pathways. Additional pathways included amino acid metabolism and glycosphingolipid metabolism. When comparing NVAMD patients to IAMD patients, 280 discriminating features were identified. Pathway analysis revealed alterations of the carnitine shuttle pathway (p<1.0 x 10-5) and the saturated fatty acid beta-oxidation pathway (p=0.048) in NVAMD patients compared to IAMD patients
These results demonstrate that fatty acid metabolism is altered in AMD patients, and these alterations are greater in NVAMD patients. This suggests that changes in fatty acid metabolism may contribute to the pathogenesis of NVAMD and represent a potential target for clinical monitoring or intervention.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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